ENST00000263413.7:c.-20-28461C>T

Variant names:

• chr5-41231711-G-A
• rs4957381
• ENST00000263413.7:c.-20-28461C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000263413.7(C6):​c.-20-28461C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,638 control chromosomes in the GnomAD database, including 25,320 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (25320 hom., cov: 31)
• Consequence: C6 ENST00000263413.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214
• Publications: 6 publications found

Genes affected

C6 (HGNC:1339): (complement C6) This gene encodes a component of the complement cascade. The encoded protein is part of the membrane attack complex that can be incorporated into the cell membrane and cause cell lysis. Mutations in this gene are associated with complement component-6 deficiency. Transcript variants encoding the same protein have been described.[provided by RefSeq, Nov 2012]

C6 Gene-Disease associations (from GenCC):

• complement component 6 deficiency

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C6	NM_001115131.4	c.-20-28461C>T		intron_variant	Intron 1 of 17		NP_001108603.2
C6	XM_011514114.4	c.8-28461C>T		intron_variant	Intron 1 of 18		XP_011512416.1
C6	XM_006714496.5	c.8-28461C>T		intron_variant	Intron 1 of 18		XP_006714559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C6	ENST00000263413.7	c.-20-28461C>T		intron_variant	Intron 1 of 17	1		ENSP00000263413.3

Frequencies

GnomAD3 genomes AF: 0.561 AC: 84937 AN: 151520 Hom.: 25318 Cov.: 31

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.578

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.560 AC: 84952 AN: 151638 Hom.: 25320 Cov.: 31 AF XY: 0.562 AC XY: 41597 AN XY: 74050

African (AFR) AF: 0.336 AC: 13883 AN: 41332

American (AMR) AF: 0.594 AC: 9043 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2085 AN: 3464

East Asian (EAS) AF: 0.558 AC: 2863 AN: 5134

South Asian (SAS) AF: 0.674 AC: 3243 AN: 4812

European-Finnish (FIN) AF: 0.635 AC: 6674 AN: 10502

Middle Eastern (MID) AF: 0.575 AC: 168 AN: 292

European-Non Finnish (NFE) AF: 0.667 AC: 45241 AN: 67848

Other (OTH) AF: 0.580 AC: 1224 AN: 2112

Alfa AF: 0.627 Hom.: 118774

Bravo AF: 0.543

Asia WGS AF: 0.586 AC: 2018 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.18
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4957381; hg19: chr5-41231813;